HIV prevention works but no single intervention alone will be enough to stop the HIV epidemic in the United States. In the absence of a magic bullet, the challenge is to identify specific program bundles and high-value targets that will squeeze the greatest possible benefit out of every prevention dollar. In 1994, our research group launched the Cost-effectiveness of Preventing AIDS Complications (or CEPAC) Collaboration, to develop a computer simulation of the clinical management, outcomes, and costs of HIV disease. We have employed the CEPAC Model to evaluate the clinical impact and cost-effectiveness of the most important developments in HIV detection, therapeutics, and prevention. In this application, we propose to use the CEPAC Model to advance three novel ways of thinking about HIV prevention program design and evaluation: viewing HIV prevention in terms of policy bundles; looking beyond program cost-effectiveness to program affordability; and designing financial incentives that translate into better long-term HIV outcomes. Our specific aims are: 1) To develop a taxonomy that characterizes the synergies and offsets that are created when prevention programs are bundled alongside one another. We will leverage the CEPAC Model to explore how the magnitude of these synergies/offsets varies with a policy bundle's scale and target population. To illustrate the usefulness of our approach, we will evaluate the cost-effectiveness of early antiretroviral therapy and HIV pre-exposure prophylaxis when used in combination with one another. 2) To conduct budget impact analysis alongside cost-effectiveness analysis. We will capitalize on the CEPAC Model's ability to assign specific costs to specific payers for specific populations, across the spectrum of HIV screening, treatment, and prevention services. To illustrate the usefulness of our approach, we will assess both the cost-effectiveness and budget impact of high-frequency HIV testing in select hot spot populations. 3) To develop a framework for categorizing and measuring the impact of financial incentives for plugging the leaks in the continuum of HIV care. We will exploit the CEPAC Model's capacity to translate/extrapolate short-run behavior change into downstream clinical and epidemic outcomes. To illustrate the usefulness of our approach, we will optimize the design of alternative incentive bundles aimed at achieving the treatment and prevention targets of the National HIV/AIDS Strategy. The broad objective that guides our research is to promote a reasoned approach to resource allocation in HIV. Our team has a proven record of disseminating findings that influence national HIV/AIDS policy. The current research plan advances the state of the art in evidence-based HIV prevention program design and evaluation.